ABSTRACT
Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.
ABSTRACT
Aim/Introduction: Persisting cerebral symptoms such as fatigue and cognitive dysfunction after Sars-CoV-2 infection are typical for post COVID-19. Positron emission tomography (PET) can contribute to the understanding of post COVID-19 related brain disorders. The aim of this study was to investigate cerebral blood flow (CBF) and neuroinflammation with PET in post COVID-19 patients. Material(s) and Method(s): Data from eight healthy controls (HC) and four subjects with post COVID-19 symptoms were included. At the time of the PET investigation, three subjects had remaining post COVID-19 symptoms, of which one had severe headache. All subjects underwent a 6 min dynamic 15O-water PET scan to measure CBF and a 60 min dynamic 11CPK11195 PET scan to measure neuroinflammation. In addition, all subjects received a T1weighted MRI that was co-registered to the PET images. Parametric images, showing 15O-water CBF and 11CPK11195 binding potential (BPND) at the voxel level, were calculated. Mean total grey matter CBF and BPND values were calculated for all subjects. The co-registered MRI images were normalized to MNI standard space using statistical parametric mapping (SPM12) and the transformation matrices were applied to the respective parametric images. A voxel-wise z-test was performed in SPM12 to compare each 15Owater CBF and 11CPK11195 BPND image from the post COVID-19 patients to the HC CBF and BPND images, respectively. A statistical threshold of p<0.05 was applied. Result(s): Two of the subjects with remaining post COVID-19 symptoms demonstrated a significantly increased CBF in the whole brain compared to the HC. Total grey matter CBF values were 1.27 and 1.41 mL/cm3/min in these two subjects, compared to a mean +/- SD of 0.65 +/- 0.19 mL/cm3/min in the HC group. The subject with persisting headache also showed large clusters of significant increased 11C-PK11195 BPND in the meninges. Mean total grey matter 11CPK11195 BPND values in post COVID-19 subjects were within the range of values in the HC group. The other two subjects did not show increased CBF and no significant increase of 11C-PK11195 BPND. Conclusion(s): Neurological symptoms from post COVID-19 may be due to increased CBF and inflammation. However, further investigations are needed with larger study cohort to better understand the relation between post COVID-19 symptoms and neurological dysfunctions investigated with PET.
ABSTRACT
Introduction: Viruses belonging to the SARS-COV family are known for their neurotropic properties. During the COVID-19 pandemic increasing data emerged, providing evidence for CNS and PNS engagement due to SARS-COV-2 infection. Cranial nerves as well as peripheral nerves have been described to be affected. According to some recent studies, a significant number of COVID-19 patients develop neurological manifestations. Method(s): We present a case of a 38-year-old woman suffering from left-sided facial pain and hypoesthesia, as well as paraesthesia, hypoesthesia, and pain in her left arm. One to two weeks prior to these symptoms, she presented with signs of upper respiratory tract infection and loss of taste and smell. She underwent a routine neurological examination and prior to her admission to the neurology ward she tested positive with qPCR for SARS-COV-2 in a nasopharynx swab. Subsequently she underwent brain and spinal MRI, analysis of cerebrospinal fluid (CSF) and neurophysiological examinations including nerve conduction studies and blink reflex analysis. Result(s): The brain and spinal MRI, CSF analysis and nerve conduction studies of the left arm (n. medianus, n. ulnaris, and the superficial radial nerve) and the facial nerve (CN VII) showed normal results. Normal blink reflex responses were obtained from both the supraorbital nerve and infraorbital nerve. When examining the mental nerve, normal responses were obtained from the asymptomatic right side but from the symptomatic left side both ipsilateral R2 and contralateral R2 responses were absent. This indicates an afferent non-specific lesion in the left mental nerve. Conclusion(s): When considering the course of her condition and excluding other probable causes, the symptoms were regarded to be related to her SARS-COV-2 infection. Hence, with this case report we can present objective neurophysiological evidence that a specific segment of the trigeminal nerve, in this case the mental nerve, can be affected by neuralgia due to COVID-19. It is notable that the patient did not present with symptoms of typical/classic trigeminal neuralgia. She was treated with carbamazepine and the facial pain was significantly improved. To the best of our knowledge, this is the first report of a pathological blink reflex associated with COVID-19. Copyright © 2022
ABSTRACT
Background: Extracellular vesicles (EVs) have been described to be associated with hemostatic disturbances in different clinical settings. (Table Presented) Aims: In this study we have investigated EVs in plasma from patients with COVID-19 in relation to the activation of coagulation. Moreover, we assessed the presence of EVs in the cerebrospinal fluid (CSF) of patients suffering neurological symptoms during COVID-19. Method(s): Eighteen patients with COVID-19 and neurological symptom admitted to the Uppsala University Hospital, Sweden were included. Median age of the patients was 64 (39-85) years, 39% were women. Twenty-one aged matched healthy individuals were included as controls. Informed consent was obtained. EVs derived from platelets (CD61+), neutrophils (MPO+) and endothelial cells (CD51/61+);together with EVs-expressing phosphatidylserine (PS+), tissue factor (CD142+), complement components C5b-9 (TCC+), C3a and C4d were determined by flow cytometry. Overall hemostasis potential (OHP), including overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) were measured and scanning electron microscopy of fibrin clots was performed. Result(s): Significantly higher OCP (p < 0.01) and OHP (p < 0.001) and lower OFP (p < 0.05) were observed in Covid-19 patients (p < 0.05), compared to controls. Denser fibrin structure was found in COVID-19 patients (Figure 1). Increased concentrations of PS+, MPO+, CD61+ and TCC+ EVs were found in plasma from Covid-19 patients compared to healthy controls, and the concentrations of PS+, CD61+ and TCC+ EVs were positively correlated with OCP and OHP in Covid-19 patients. The presence of CD61+, CD51/61+, MPO+ EVs and EVs exposing PS and TCC was identified in the CSF obtained from 17 patients (Figure 2). Conclusion(s): Procoagulant state together with elevated levels of circulating EVs of different cell origin was found in patients with Covid-19. The unique finding of this study is the presence of EVs in CSF of Covid-19 patients with neurologic manifestations. EVs may represent potentially novel biomarkers of blood-brain barrier damage during SARS-COV- 2 infection.